Type I collagen is the major structural macromolecule of skin representing more than 85% of its collagen content. Abnormalities in synthesis of type I collagen have been reported in several inherited disorders of connective tissue including Marfan syndrome, Ehlers-Danlos syndrome, osteogenesis imperfecta and cutis laxa. In order to develop the tools necessary to study these diseases at a molecular level and understand the cellular regulation of collagen biosynthesis we have undertaken the isolation of collagen genes. Type I collagen is composed of two polypeptide chains each of which is a separate gene product. We have isolated from a human genomic library two overlapping fragments comprising approximately one half of the genome for pro alpha2(I). We proposed to isolate and characterize the entire pro Alpha2(I) gene as well as the gene for pro Alpha1(I). A detailed structural map of these genes will provide us with the background information needed to precisely understand structural gene mutations in inherited connective tissue disorders. In addition we propose to construct specific single stranded probes for hybridization measurements of initial transcript RNA as well as mRNA in cell culture experiments designed to investigate regulation of collagen synthesis.